I recommend CNS Neurological Disorders & Drug Targets to neuroscientists and practicing neurologists. The papers published on this platform are always of sufficient merit and quality. It maintains the highest standards of peer review, preserving the integrity of science.

Metabolic Stress and Inflammation: Implication in Treatment for Neurological Disorders

Although the impact of metabolic disorders (obesity, diabetes etc.) on physical health is widely
recognized, a recent and growing body of research showed that this pathology is also associated
with cognitive impairment, deficits in learning, memory and executive functioning, and
increased incidence of neuropsychiatric disorders. On the other hand, stressful life events deeply
impact on brain and bodily function and, in addition to representing major risk factors for
neuropsychiatric disorders, also influence energy metabolism and feeding control. Indeed, while
acute stress rapidly induces hyperglycemia, prolonged increased glucocorticoids stimulate
appetite and increase gluconeogenesis and fat storage. Considering the global aging of world
population and the increased prevalence of metabolic disorders and Neuropsychiatric Disorders,
a better comprehension of pathophysiological mechanisms of these disorders in aging has
become crucial for better prevention, diagnosis and treatment. Moreover besides above, recent
evidence has implicated neuroinflammation and endoplasmic reticulum (ER) stress as
components of a novel form of neuronal metabolic stress that develop in neurological disorders
and peripheral nervous system dysfunction over the time. Among the possible underlying
mechanisms whereby both metabolic stress and inflammation impair peripheral as well as higher
neuronal functions and exacerbate neurological disorders. Given the high incidence of
comorbidity and linked etiology, there is urgent need to focus the latest development on the said
area.
Therefore, in the proposed special issue for CNS and Neurological Disorders - Drug Target,
entitled “Metabolic Stress and inflammation: Implication for Treatment of Neurological
Disorders”, we will try to assimilate the available knowledge and understanding on the topic.
The volume will be a very useful treatise to students, basic researchers, and clinicians alike.

Potassium Channels and CNS Diseases

In central nervous system (CNS), ion channels, especially potassium channels play important regulatory roles in physiological
processes. Potassium (K+) channels (e.g., voltage-gated K+ channel, calcium-activated K+ channel) can be activated by
membrane potential shift as well as various ligands [1]. K+ channels have widely relationship with CNS diseases. Although
many studies have tried to reveal the effect of K+ channels in CNS diseases [2-5], the underlying mechanisms are not clearly
elucidated, because of the various subfamilies and subtypes of K+ channels.
In physiological condition, K+ channels mainly elicit an inhibitory modulation in central nervous system. Functional deficiency
or expressional down-regulation of K+ channels may enhance neuronal excitability, induce pathological condition, and
thus leads to CNS diseases, such as epilepsy [3]. The suppression of G protein-gated K+ (GIRK) channels are related to the
pathogenesis of Parkinson’s disease, drug addiction, cerebellar ataxia, pain and analgesia [4]. Some K+ channels can also control
the local microenvironment by regulating the extracellular K+ concentration.
This thematic issue has reviewed those research works describing the experimental discoveries, as well as the pathological
effect of K+ channels. In addition, some reviews in this thematic issue also summarized other ion channels, such as Na+ channels,
Ca2+ channels, Cl- channels, transient receptor potential cation (TRP) channels and synaptic receptors (AMPA, NMDA,
GABA receptors), concentrating on their correlationship with K+ channels and CNS diseases.
First of all, Zang K. et al. [6] and Zhu Y. et al. [7] focused on the large conductance calcium-activated K+ (BK) channels,
and retrospected the most recent scientific literature on the structure, subunits and locations of BK channels, broadly describing
the functional effects of different BK types on neurons, astrocytes, microglias, oligodendrocytes and smooth muscle cells. After
that, two reviews both concentrated on the modulation of BK channels on the epilepsy, and discussed the possibility of developing
potential antiepileptics targeted on different BK subunits. In the conclusion, the authors optimistically prospected that the
SNPs (single nucleotide polymorphisms) of KCNMA1 and KCNMBs might be the future investigation targets of BK channel
dysfunction, and optogenetic technique could be helpful to suppress the epileptic seizures [6-7].
Gao F. et al. [8] and Feng X. et al. [9] more specifically evaluated recent research papers on particular K+ channels. Gao et
al. reviewed those K+ channels in Müller glial cells, which located on the retina and related to the retinal disorders, including
retinal ischemia-reperfusion, diabetic retinopathy, inherited retinal dystrophy, retinal detachment, proliferative vitreoretinopathy
and glaucoma. These retinal K+ channels, such as BK channel, delayed rectifier K+ channel (KDR) and A-type K+ channel,
keep the hyperpolarized potential and contribute to retinal neuronal damage in pathological conditions, which may serve as
potential targets to develop new therapeutic approaches in the future [8].
Feng et al. reviewed the functions and pathological relations of lysosomal K+ channels with neurodegenerative diseases,
which were also called lysosomal storage diseases (LSDs). Lysosomal BK channel and transmembrane protein 175
(TMEM175), a novel lysosomal K+ channel, have been reviewed in this paper, describing their structure, expression on
lysosomal plasma membrane, modulation effects on Ca2+ signaling and lipid metabolism. Dysfunction of lysosomal BK channels
and TMEM175 elicits LSD-related Fabry disease and Hunter syndrome, which can be rescued by specific K+ channel agonists
[9].
Yang J. et al. [10] reviewed the oxidation of K+ channels in neurodegenerative diseases, such as Alzheimer’s disease (AD)
and Parkinson’s disease (PD). This short review elucidated the damages of different K+ channels caused by reactive oxygen
species (ROS). Oxidation of KV2.1, KV3.4, KV4.3, BK, KATP and organellar K+ channel causes the abnormal features such as
mitochondrial dysfunction, oxidative stress and autophagy compromise, which will result in collapse of intracellular homeostasis
and eventually leads to cell death [10].
In this thematic issue, Wu X. et al. [11] and Yan R. et al. [12] reported their experimental findings on inwardly rectifying
K+ (Kir) channels, both through patch clamp electrophysiological recordings. Wu et al. affirmed that tenidap, an inhibitor of
cyclooxygenase / arachidonate 5-lipoxygenase (COX/5-LOX), served as the opener of Kir2.3 channel and possessed antiepileptic
effect in cyclothiazide induced epileptiform seizures [11]. Meanwhile, Yan et al. reported that Jingshu Keli, a herbal formula
of traditional Chinese medicine (TCM), alleviated the mechanical and thermal symptoms of cervical spondylotic myelopathy
by increasing the phosphorylation level of Kir3.1 [12]. These two works are the only original researches in this thematic issue,
which may enhance the value and significance of this thematic issue, on contributing the advancement of knowledge in K+
channels.
Here we mention the TCMs, which represent a large group of medicinal compounds derived from plants and other natural
sources. Those studies of the effects of TCMs on different K+ channels provide new insights on the pharmacognostic aspects to
research K+ channels and CNS diseases. Recent studies have detected several compounds from TCMs that serve as novel K+
channel modulators, for example, curcumin (from Curcuma longa) as blocker to KV1.3, KV1.4, KV2.1 channels [13-15], puerarin
(from Pueraria lobata) as inhibitor to Kir2.1, Kir2.3, KV7.1 channels [16]. In the study from Yan et al., two saponins, ginsenoside
Rb1 (GRb1) and notoginsenoside R1 (NGR1), were also found that acted as an antagonist to Kir currents [12].
To further investigate the modulation of TCMs on K+ channels and other ion channels, Huang Y. et al. was then provided a
review elucidating the recent studies of TCMs and ion channel [17]. In this review, several TCM herbs and their containing
active ingredients were introduced, including Salvia miltiorrhiza Radix et Rhizoma, Ligusticum chuanxiong Rhizoma, Angelica
sinensis Radix, Panax ginseng Radix et Rhizoma, Panax notoginseng Radix et Rhizoma, Uncaria rhynchophylla Ramulus Cum
Uncis, Scutellaria baicalensis Radix and so on [17].
Finally, Zhou Y. et al. [18] and Feng Y. et al. [19] focused on the voltage-gated Na+ channels (VGSCs) and reviewed their
functional relationship to CNS diseases from recent scientific literature. Zhou et al. discussed the roles of VGSCs in the processing
of sensory information, including auditory sense, visual sense, olfactory sense, tactile sense and taste sense, as well as
related disorders caused by the dysfunction of VGSCs [18]. Meanwhile, Feng et al. retrospected the mutations of VGSC
subunits both on the aspects of genotypes and phenotypes, and introduced specific CNS diseases elicited by VGSC mutations,
especial the epilepsy. In this review, those mutations located on SCN1A (NaV1.1), SCN2A (NaV1.2), SCN3A (NaV1.3),
SCN8A (NaV1.6) and SCN9A (NaV1.7) were described [19]. These two reviews were included into this thematic issue to exhibit
the similarities and differences between Na+ channels and K+ channels, as well as their correlations, in the pathology of
CNS diseases.
We hope that this special issue represents a valuable contribution to understand the roles of different K+ channels, as well as
other ion channels, in the pathogenesis of CNS diseases like epilepsy.

Advances in Therapies of Cerebellar Disorders

Cerebellar ataxias (CAs) gather a group of disorders characterized by motor incoordination and impaired
cognitive operations. Rapid developments in novel technologies offer now a real possibility to improve CAs.
Typical examples are molecular targets for stopping degeneration, grafted stem cells to protect degenerating
host cells, and non-invasive cerebellar stimulation to manipulate excitability in a residual cerebellar circuits
in order to improve CAs. In addition, there has been accumulating clinical evidence for therapeutic efficacies
of novel anti-CAs drug such as aminopyridines, and therapies on immune-mediated CAs. Improved
protocols have also been proposed in the field of motor rehabilitation.
These basic and clinical advances have opened a door to a new era where neuroscientists and clinicians will
control the process of cell death and restore impaired cerebellar functions. We aim to gather top reviews to
examine hierarchically the progresses in therapies of CAs in terms of identification of molecular targets,
understanding of cell biology, neural circuits and clinical evidence of effectiveness of new therapies. We will
consider therapeutic strategies not only for the interruption of the disease progression but also for the
restoration of lost cerebellar functions.